The prevalence of atrial fibrillation in the US is approximately 2.7 to 6.1 million, putting patients at significantly increased risk of cardioembolic stroke. Approximately 15-20% of all strokes are caused by atrial fibrillation. Most atrial fibrillation is treated with blood thinners, however some patients are at such high risk of bleeding that it prohibits anticoagulation. Left atrial appendage closure devices (LAAC) have been developed to reduce the risk of clot embolism, but they still require blood thinner use for at least 45 days, until the device interface has been covered by a healthy endothelial lining. Endomimetics has developed a nanomatrix coating that enhances endothelial coverage, and inhibits inflammatory responses and blood clot formation. This nanomatrix can be coated on a LAAC device, releasing nitric oxide (NO) over 2 months, enhancing endothelialization and neoendocardium formation. The nanomatrix coating is a biocompatible peptide based material that is coated on the LAAC device by simple water evaporation. More rapid healing could significantly shorten the duration of required blood thinner therapy. In this Phase I SBIR, we propose to evaluate and optimize the coating for LAAC devices. This will include evaluation of physical characteristics and assessing effects on endothelial cell growth and migration, as well as platelet adhesion. In collaboration with Boston Scientific, we will then evaluate the nanomatrix-coated LAAC devices in vivo, in an established canine LAAC model. Developing a coating that promotes LAAC closure may have significant impact for the treatment of patients with atrial fibrillation who are at high risk for anticoagulation. With successful completion of Phase I, we plan to move forward in Phase II to larger scale GLP studies.